Reduction of retrovirus-induced immunosuppression by in vivo modulation of T cells during acute infection |
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Authors: | He Hong Messer Ronald J Sakaguchi Shimon Yang Guojun Robertson Shelly J Hasenkrug Kim J |
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Institution: | Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. |
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Abstract: | Chronic infection with Friend retrovirus is associated with suppressed antitumor immune responses. In the present study we investigated whether modulation of T-cell responses during acute infection would restore antitumor immunity in persistently infected mice. T-cell modulation was done by treatments with DTA-1 anti- glucocorticoid-induced tumor necrosis factor receptor monoclonal antibodies. The DTA-1 monoclonal antibody is nondepleting and delivers costimulatory signals that both enhance the activation of effector T cells and inhibit suppression by regulatory T cells. DTA-1 therapy produced faster Th1 immune responses, significant reductions in both acute virus loads and pathology and, most importantly, long-term improvement of CD8(+) T-cell-mediated antitumor responses. |
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